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Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models

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Abstract

Introduction

Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos (main component silibinin), from the milk thistle plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models.

Methods

One wound healing and three tumor studies were performed. Tumor Study (TS)1 assessed the impact of PES on subcutaneous tumor growth, whereas TS2 assessed PES’s impact on subcutaneous growth when given pre- and post-CO2 pneumoperitoneum (pneumo), sham laparotomy, or anesthesia alone. TS3 determined the ability of PES to limit hepatic metastases (mets) after portal venous injection of tumor cells. In the final study, laparotomy and gastrotomy wound healing were assessed several ways. BALB/c mice were used for all studies. The drugs were given via drinking water (PolyE) and gavage (Siliphos), daily, for 7–9 days preprocedure and for 7–21 days postoperatively. Tumor mass, number/size of hepatic mets, and proliferation and apoptosis rates were assessed. The abdominal breaking strength and energy to failure were measured postmortem as was gastric bursting pressures.

Results

PES significantly inhibited subcutaneous growth in the nonoperative setting. PES also significantly decreased the number/size of liver mets when given perioperatively. Abdominal wound breaking strength, energy to wound failure, and collagen content were not altered by PES; gastrotomy bursting strength also was not affected by PES. Neither drug alone had a significant impact on tumor growth.

Conclusions

The PES combination inhibited subcutaneous and hepatic tumor growth yet did not impair wound healing. PES holds promise as a perioperative anticancer therapy.

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Acknowledgement

This project was funded by Society of American Gastrointestinal and Endoscopic Surgeons (SAGES, grant #2009043). We greatly appreciate the support.

Disclosures

Xiaohong Yan, Thomas R. Gardner, Michael Grieco, Sonali A.C. Herath, Joon Ho Jang, Daniel Kirchoff, Linda Njoh, H.M.C. Shantha Kumara, Samer Naffouje, and Richard L. Whelan have no conflicts of interest or financial ties to disclose.

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Authors and Affiliations

  1. Colon & Rectum Surgery, St. Luke’s Roosevelt Hospital Center, 432 West, 58th Street, Room 517, New York, NY, 10019, USA

    Xiaohong Yan, Sonali A. C. Herath, Joon Ho Jang, Daniel Kirchoff, Linda Njoh, H. M. C. Shantha Kumara & Samer Naffouje

  2. Orthopaedic Surgery, Columbia University, 630 West, 168th Street, Black building 14th Floor, New York, NY, 10032, USA

    Thomas R. Gardner

  3. Surgery, Saint Barnabas Medical Center, 94 Old Short Hills Road, Livingston, NJ, 07039, USA

    Michael Grieco

  4. Colon & Rectum Surgery, St. Luke’s Roosevelt Hospital Center, 425 West, 59th Street, Suite 7B, New York, NY, 10019, USA

    Richard L. Whelan

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Correspondence to Richard L. Whelan.

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Yan, X., Gardner, T.R., Grieco, M. et al. Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models. Surg Endosc 26, 1856–1864 (2012). https://doi.org/10.1007/s00464-011-2114-2

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